The skin is a complex membrane that performs many physiological functions such as metabolism, synthesis, temperature regulation, and excretion. Its upper layer, the stratum corneum, is considered to be the main barrier to the percutaneous penetration of exogenous materials.
There are several categories of pharmaceutical products which are targeted to the skin or utilize the skin as a port of entry into the body. These include transdermal and topical drug delivery systems (patches), gels, creams, ointments, lotions, as well as subcutaneous implants and dermal vaccinations. As with other routes of delivery, transport into and across the skin is also associated with several disadvantages mainly that not all drugs are suitable candidates.
A number of physicochemical parameters have been identified, such as molecular hydrophobicity, size, and the ability to interact with the other molecules, e.g. hydrogen bond formation that influence the diffusion process, and variations in permeation rates can occur between different skin models, patients, different races, and between young and old. The major challenge is overcoming the resistance of the skin to perneation in a reversible and non-damaging manner, as well as the design of therapeutically effective topical and transdermal formulations.
The development of topical and transdermal drug delivery systems has been aimed at overcoming the remarkably efficient barrier property of human skin by nontoxic and non-irritant methods. Numerous chemical and physical approaches have been investigated to overcome the skin's formidable barrier function and can be divided into passive or active methods. Active methods of enhancing skin permeation include techniques such as iontophoresis (electrical approach), use of microneedles (mechanical approach), ultrasound, laser and photomechanical waves. Passive methods include use of penetration enhancers, liposomes, or other vehicles, prodrug or metabolic approach, enhancement of the driving force of drug diffusion (thermodynamic activity), and/or increasing the permeability of the skin.
The choice of formulation is also important in order to obtain a suitable profile in terms of solubility/dispersability and stability of the drug. The most functional formulation should be able to solubilise both hydrophobic and hydrophilic substances and at the same time increase uptake efficiency without causing notable damage to the skin. An additional challenge in topical delivery to the skin is the limited number of suitable drugs which are generally reduced to small, moderately lipophilic and highly potent ones. In general, highly lipophilic molecules do not transfer well from the mainly lipidic stratum corneum into the more aqueous viable epidermis and, as a result, are often poorly permeable.
Several strategies for improving cutaneous delivery, including complex physical enhancement methods, for example, iontophoresis, sonophoresis, and electroporation, have been developed, however these techniques are more suited to hydrophilic, water-soluble substances. With respect to passive enhancement methods, supersaturated formulations or novel vehicle systems, for example, microemulsions, liposomes, and colloidal polymeric suspensions, have also been investigated as alternatives to the more “classic” chemical penetration enhancer systems. A limited number of biodegradable, polymer microparticles and solid-lipid nanoparticles have been investigated with respect to their potential for transdermal drug administration. Nevertheless the percutaneous penetration of highly lipophilic molecules remains problematic and need for a suitable delivery vehicle is in demand.